An association of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and common carotid atherosclerosis

Plasma homocysteine (Hcy) concentration has been shown to be influenced by a mutation in the gene coding methylenetetrahydrofolate reductase (MTHFR). Although plasma Hcy is related to atherosclerotic disorders, conflicting re sults have been reported about the association between MTHFR gene polymorph ism and sclerotic lesions of the common carotid arteries. The effect of age -gene interaction on carotid arterial remodeling was investigated in elderl y subjects with several risk factors for atherosclerosis. We evaluated scle rotic lesions of the common carotid arteries by ultrasonography in 326 pati ents (mean age +/- standard deviation, 73 +/- 12 years) and studied relatio ns among the known risk factors for atherosclerosis, including MTHFR gene p olymorphism and its interactions with age and sex. Of the 326 subjects stud ied, 136 had MTHFR genotype CC, 136 genotype CT. and 54 genotype TT. The th ree groups did not differ with respect to background factors such as age, h istory of cigarette smoking, blood pressure, lipids or uric acid. or in the incidence of atherosclerotic diseases. Spearman's rank correlation reveale d a significant relationship between gender. age, Brinkman index. systolic blood pressure, triglycerides, HDL-cholesterol (HDL-C). uric acid, and MTHF R gene polymorphism. Multiple regression analysis using intimamedia complex thickness (IMT) as a criterion variable and risk factors. including MTHFR gene polymorphism as explanatory variables showed that MTHFR gene polymorph ism (P = 0.039) was a significant independent explanatory variable for IMT. along with gender (male) (P < 0.001), age (P < 0.001), systolic blood pres sure (SBP) (P = 0.047), total cholesterol (T-C) (P < 0.001), and HDL-C (P < 0.001). Furthermore. a general linear model analysis revealed that interac tion between age and MTHFR gene polymorphism was significantly associated w ith IMT, independently of age, SBP, T-C, and HDL-C in male subjects. Howeve r. age-gene interaction was not observed in female subjects. The findings o f the present study confirm an association between MTHFR gene polymorphism and common carotid atherosclerosis in the Japanese population and further s upport the role of risk factor-gene interaction in common carotid atheroscl erosis.